Journal article
Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis
The Journal of clinical investigation, Vol.107(10), pp.1275-1284
05/15/2001
Handle:
https://hdl.handle.net/2376/108887
PMCID: PMC209294
PMID: 11375417
Abstract
Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules would provide a new immunotherapeutic strategy for autoimmune and other diseases. We have engineered bone marrow–derived DCs that express IL-4 and tested the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4–transduced DCs inhibited Th1 responses to collagen type II in vitro. A single injection of IL-4–transduced DCs reduced the incidence and severity of CIA and suppressed established Th1 responses and associated humoral responses, despite only transient persistence of injected DCs in the spleen. In contrast, control DCs and IL-4–transduced T cells or fibroblastic cells failed to alter the course of the disease. The functional effects correlated well with the differential efficiency of DC migration from various sites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4–transduced DCs. These results support the feasibility of using genetically modified DCs for the treatment of autoimmune disease.
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Details
- Title
- Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis
- Creators
- Yoshitaka Morita - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterJianmin Yang - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterRaj Gupta - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterKoichi Shimizu - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterEric A Shelden - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterJudith Endres - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterJames J Mulé - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterKevin T McDonagh - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases CenterDavid A Fox - Division of Rheumatology, Department of Internal Medicine; and Multipurpose Arthritis and Musculoskeletal Diseases Center
- Publication Details
- The Journal of clinical investigation, Vol.107(10), pp.1275-1284
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Clinical Investigation
- Identifiers
- 99900547230301842
- Language
- English
- Resource Type
- Journal article